title: Synthesis and structure-activity relationship of mono-indole-, bis-indole-, and tris-indole-based sulfonamides as potential anticancer agents.
abstract: A series of arylsulfonyl mono-indoles (10-15), bis-indoles (16-27), and tris-indoles (28-32) have been synthesized and evaluated for their cytotoxicity toward four human cancer cell lines including HuCCA-1 (cholangiocarcinoma), HepG2 (hepatocellular carcinoma), A-549 (lung carcinoma), and MOLT-3 (lymphoblastic leukemia). Most of the synthesized indoles displayed cytotoxicity against the MOLT-3 cell line except for analogs 16, 17, and 32. Significantly, the [Formula: see text]-sulfonylphenolic bis-indole series (18-27) and the [Formula: see text]-chlorobenzenesulfonyl tris-indole (30) showed higher antiproliferative activity against HepG2 cell than the reference drug, etoposide. Promisingly, the [Formula: see text]-chlorobenzenesulfonyl bis-indole (20) and tris-indole (30) provided 3-fold and 2-fold stronger activity, respectively, against HepG2 cell than etoposide. Moreover, the phenolic bis-indole (20) was also shown to be the most potent cytotoxic agent against HuCCA-1 and A-549 cell lines with [Formula: see text] values of 7.75 and [Formula: see text], respectively. The tris-indole analogs 28, 29, and 31 also exhibited selectivity against MOLT-3 cell. The findings disclosed that [Formula: see text]-arylsulfonyl bis-indoles-bearing phenolic groups are potentially interesting lead pharmacophores of anticancer agents that should be further investigated in more detail.
authors.affiliation: Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, 10110, Thailand. ratchanok@swu.ac.th
authors.forename: Ratchanok
authors.initials: R
authors.lastname: Pingaew
authors.forename: Supaluk
authors.initials: S
authors.lastname: Prachayasittikul
authors.forename: Somsak
authors.initials: S
authors.lastname: Ruchirawat
authors.forename: Virapong
authors.initials: V
authors.lastname: Prachayasittikul
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001190:Arylsulfonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001190:Arylsulfonates; D007211:Indoles; D013449:Sulfonamides